Acute Kidney Injury in Severe Malaria: A Serious Complication Driven by Hemolysis

Abstract

Acute kidney injury (AKI) is a common clinical complication in malaria, with AKI reported across all species that cause severe disease, including Plasmodium falciparum, Plasmodium knowlesi, and Plasmodium vivax. AKI during malaria varies based on host and parasite factors, including the growth potential of the parasite within host red blood cells, the extent of red blood cell lysis, and the capacity of the parasite to sequester within the microvasculature. In this review, we focus primarily on P. falciparum pathogenesis and the role of intravascular hemolysis in AKI through the depletion of endogenous hemoglobin and heme scavengers, resulting in oxidative stress and tissue injury. We discuss the etiology of blackwater fever as a hemolytic complication in severe malaria that has been rising in incidence. All patients with severe malaria should have a high index of suspicion for AKI, particularly when hemolytic features are present. Finally, we review potential interventions to mitigate the impact of hemolysis on kidney injury in severe malaria. Given the high burden of malaria in Africa, the incidence of AKI in severe malaria, and the number of malaria episodes over a person's lifetime, the cumulative impact of malaria-associated AKI on chronic kidney disease needs to be considered. Semin Nephrol 36:x-xx © 20XX Elsevier Inc. All rights reserved.

Keywords: Severe malaria; acute kidney injury; cell-free hemoglobin; hemolysis; oxidative stress.